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The majority of viruses have protein containers, called capsids, in which proteins are arranged with icosahedral symmetry. The capsids of these viruses follow structural blueprints that can be modelled as subsets of 3-dimensional aperiodic lattices called quasicrystals. These, in turn, can be obained by projection from 6-dimensional Bravais lattices. In this work we apply the crystallographic theory of phase transitions to these 6D lattices, and via projection of these results derive information on the structural transitions of viruses important for infection.

This paper traces the beginnings of structural virology, from the early 1950's to the presentation of the Caspar-Klug theory of virus structure in 1962. It focuses primarily on the virus research of Francis Crick, James Watson, Rosalind Franklin, Aaron Klug, and Donald Caspar. Collaborative efforts in X-ray crystallography and electron microscopy in combination with intellectual triggers from the Art world provided the soil from which the early theories of virus structure grew and matured.

New findings challenge our understanding of the alpha virus structure and fusion mechanism. It is evident from recent work in electron cryomicroscopy, cryoEM, that the external domains of the membrane-anchored glycoproteins, E1 and E2, form a shell at some distance above the membrane. From there, the glycoproteins protrude further outwards as three-lobed spikes. They present a receptor-binding site residing in E2 at their outermost domains, distal to the center of the spike. The ectodomain of the fusion protein, the E1, has an elongated shape, as revealed by X-ray crystallography. Fitted in the cryoEM structure of the virus, the C-terminal and central parts of the E1 ectodomain fill the major portion of the shell, while the fusion peptide loop hides under the receptor-binding domain in the spike. With this structural background, the alphaviruses represent an intriguing new fusion principle, differing in many aspects from the established influenza model. This mechanism is now on its way to be revealed.

Macromolecular assemblies, like viruses, are often built by multiple copies of a few components. These may have similar or diverse functions. The multivalency of the assembly allows ligand recognition with high avidity. Nevertheless, affinity is linked to the monovalent ligand interaction, related to the nature of the interactive surface. Such interactions can be followed in real time by the aid of surface plasmon resonance. Thus a sensor surface may be prepared with either the assembly or the ligand immobilized at the sensor and their interaction studied. Kinetic and thermodynamic properties of ligand binding to the macro-molecular assembly can be determined. Variations in the structure of the assembly, like those occurring during virus infection may also be revealed by this technique.

Virus structures represent mega-molecular nucleoprotein complexes. The three dimensional structures of 74 unique virus capsids, from 21 families and 30 different genera, have been determined at near atomic resolution. We have devised a website and a database of high-resolution virus structures namely VIrus Particle ExploreR (VIPER: http://mmtsb.scripps.edu/viper/) as a repository of virus structures, where all the structures are stored in a single (standard) icosahedral convention. Each capsid is shown pictorially along with a list of the physical properties. Furthermore, the derived results of structural and computational analyses on each capsid are provided highlighting the inter-subunit residue-residue contacts, binding energies, quasi-equivalence and assembly pathways. The structural and analysis tools developed to analyze virus structures can be accessed through the VIPER web site. Efforts are ongoing to include cryo-EM reconstructions as well as the models fitted into these densities.